This project is directed to af understanding of the structure and function of CNS myelin. The major thrust of the program is towards the chemical characterization of bovine white matter proteolipid and the determination of its primary structure. The program requires the preparation of chemically modified proteolipids, the controlled chemical and enzymatic cleavage of the protein and separation and purification of sufficient amounts of peptides for sequencing. High performance liquid chromatography will be among the methods used for the separation of peptides and the identification of derivatives obtained during sequencing. In the course of these studies information on the chemical properties of the protein will be obtained. Comparable sequence studies will be carried out on proteolipids from other animal species, from various regions of the nervous system and on pathological material. A second aspect of the program involves the study of lipid-protein interactions in myelin. The sequencing techniques provide methods for determining the precise site of attachment of covalently bound fatty acid to the protein. Dynamic aspects of protein-lipid interactions will be investigated as part of a project on the factors controlling the activity of myelin carbonic anhydrase. The lipid composition of myelin carbonic anhydrase and the effect of lipids on the activity of the enzyme will be studied. These projects are part of a long range effort to understand the factors controlling myelin stability and their alterations in demyelinating diseases such as multiple sclerosis.